Differences in the pattern of regulation of homologous genes in related species are of interest in at least two contexts: they provide tools that can be used to analyze mechanisms of gene regulation and they may be important to our understanding of the process of evolution. Within the rapidly evolving picture-winged group of Drosophila, various species display dramatically different patterns of regulation of a small set of non-essential enzymes involved in degradation of environmentally-derived substrates. The current project will investigate the generality of this finding. Comparison of patterns of regulation of the same set of enzymes in an evolutionarily conservative group of Drosophila should provide an indication as to whether rapid change in gene regulation is specifically related to rapid morphological and ecological diversification. Examination of a selected set of enzymes with quite different metabolic roles and of a large set of randomly chosen gene products will indicate whether extensive regulatory variability is a property of a wide range of gene products or is specific to the category of enzyme previously studied. Patterns of enzyme expression will be determined by standard electrophoretic analysis of dissected tissues. Regulation of other genes will be characterized by measuring hybridization of mRNA from various tissues and stages to randomly chosen cloned cDNAs. Variability of gene regulation within species and the frequency and distribution of regulatory polymorphisms in natural populations will be examined by similar methods. This work can contribute conceptually to several health related problems. Many hereditary diseases that do not have a known basis in a defective gene product may result from abnormal timing or level of gene expression. These studies may provide models for such conditions. Some cancers apparently result from abnormal expression of specific genes (oncogenes). Any contribution to our understanding of mechanisms of gene regulation is potentially important. Finally, development of drug or pesticide resistance in populations of pathogens or disease vectors may involve evolution of modified expression of existing genes. This would be entirely analogous to the phenomena which are the subject of this project.